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Neuro Oncol. 2013 May;15(5):548-61. doi: 10.1093/neuonc/nos388. Epub 2013 Feb 14.

CRN2 enhances the invasiveness of glioblastoma cells.

Author information

1
Center for Biochemistry, Institute of Biochemistry I, Medical Faculty, Hamburg, Germany.

Abstract

BACKGROUND:

Movement of tumor cells involves dynamic remodeling of the actin cytoskeleton, which is regulated by actin binding proteins, such as CRN2 (synonyms: coronin 1C, coronin 3). In vitro, CRN2 participates in secretion, matrix degradation, protrusion formation, and cell migration. Furthermore, expression of CRN2 correlates with the malignant phenotype of human diffuse gliomas. CRN2's effects on actin polymerization and F-actin bundling are abolished by protein kinase 2 (CK2) dependent phosphorylation at serine 463.

METHODS:

We generated human U373 glioblastoma cell lines with knock-down of CRN2 or over-expression of CRN2 variants and studied their behavior in vitro and ex vivo in organotypic brain slice cultures.

RESULTS:

CRN2 over-expression and expression of the S463A phospho-resistant CRN2 variant increase proliferation, matrix degradation, and invasion but decrease adhesion and formation of invadopodia-like extensions in vitro. Knock-down of CRN2 and expression of S463D phospho-mimetic CRN2 generally have opposite effects. Analysis of invadopodia-like cell extensions shows a diffuse relocalization of F-actin in CRN2 knockdown cells, whereas expression of S463A and S463D mutant CRN2 causes enrichments of F-actin structures at the center and rime zone, respectively. Fluorescence recovery after photobleaching studies of CRN2 and F-actin in lamellipodia show that both CRN2 variants decrease the turnover of actin filaments. Glioblastoma cells over-expressing wild-type or S463A CRN2, which were transplanted onto brain slices, characteristically developed into tumors with an invasive phenotype.

CONCLUSIONS:

Overall, our data indicate that CRN2 participates in cancer progression via modulation of the actin cytoskeleton.

PMID:
23410663
PMCID:
PMC3635520
DOI:
10.1093/neuonc/nos388
[Indexed for MEDLINE]
Free PMC Article

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